Anticonvulsant and antiarrhythmic effects of nifedipine in rats prone to audiogenic seizures

Abstract

Calcium ion participates in the regulation of neural transmission and the presynaptic release of neurotransmitters. It is also involved in epileptic events, cardiac arrhythmias and abnormal conduction of stimuli. The purpose of the present study was to evaluate the effects of nifedipine, a calcium channel blocker, on epileptic seizures and on reperfusion arrhythmias in rats prone to audiogenic epileptic seizures (Wistar audiogenic rats, WAR) and in normal Wistar rats (N = 6/group). The seizure severity index was applied after an intraperitoneal injection of 20 or 40 mg/kg nifedipine (N20 and N40 groups, respectively). The Langendorff technique was used to analyze cardiac function, as well as the incidence and severity of the reperfusion arrhythmias after ligature and release of the left coronary artery in rats treated or not with nifedipine. We found that nifedipine treatment decreased seizure severity (0.94 ± 0.02 for WAR; 0.70 ± 0.10 for WAR + N20; 0.47 ± 0.08 for WAR + N40) and increased the latent period (13 ± 2 s for WAR; 35 ± 10 s for WAR + N20; 48 ± 7 s for WAR + N40) for the development of seizures in WAR. Furthermore, the incidence and severity of the reperfusion arrhythmias were lower in WAR and normal Wistar rats injected with nifedipine. In WAR, these effects were mediated, at least in part, by a decrease in heart rate. Thus, our results indicate that nifedipine may be considered to be a potential adjuvant drug for epilepsy treatment, especially in those cases associated with cardiac rhythm abnormalities.

Figure 1.. Severity index of seizures in Wistar audiogenic rats (WAR) treated or not with 20 or 40 mg/kg nifedipine (N20 or N40). Data are reported as means ± SEM for 6 rats per group. ^*P < 0.05 compared to untreated animals (WAR) (Kruskal-Wallis test followed by the Dunn post-test).

Figure 2.. Effects of 20 and 40 mg/kg nifedipine (N20 and N40) on the heart rate of isolated hearts of A, Wistar rats and B, Wistar audiogenic rats (WAR). Data are reported as means ± SEM for 6 rats per group. ^*P < 0.05 compared to control (Wistar or WAR) (one-way ANOVA followed by the Newman-Keuls post-test).

Figure 3.. Effects of 20 and 40 mg/kg nifedipine (N20 and N40) on the duration of reperfusion arrhythmias in isolated hearts of A, Wistar rats and B, Wistar audiogenic rats (WAR). Data are reported as means ± SEM for 6 rats per group. ^*P < 0.05 compared to control (WAR) (one-way ANOVA followed by the Newman-Keuls post-test).